This is a continuation of PCT/EP99/01853 filed Mar. 19, 1999.
The present invention relates to antibacterial compounds which are 7-acylamino-3-(cyclic aminoguanidine)methylene cephalosporins, including 3-cyclic aminoguanidine-like structured compounds having a triamino-methylidyne group instead of an aminoguanidine group.
In one aspect the present invention provides a compound of formula 
wherein
W denotes CH or N,
V denotes CH or NO,
R1 denotes hydrogen, acyl, carboxyl or alkyl,
R3 denotes hydrogen or an ester moiety,
R2 denotes a group of formula 
xe2x80x83wherein
X and Y independently of each other each denote (C2-5)alkylene, or (C2-5)alkenylene
wherein one xe2x80x94Cxe2x95x90Cxe2x80x94 double bond is present, or, in case of at least C4-alkenylene,
wherein two xe2x80x94Cxe2x95x90Cxe2x80x94 double bonds are present,
R4 denotes hydrogen or alkyl,
R5 denotes hydrogen, alkyl, or aminoiminomethyl,
R6 denotes hydrogen, alkyl, cycloalkyl, amino, hydroxy, alkoxy, heterocyclyl or a group of formula xe2x80x94Nxe2x95x90CHR8, wherein
R8 denotes alkyl, aryl or heterocyclyl, or
R5 and R6 together with the nitrogen atoms to which they are attached denote heterocyclyl,
Rxe2x80x26 denotes alkyl,
R7 denotes hydrogen, or
R6 and R7 together with the nitrogen atom to which they are attached form heterocyclyl.
In formula I R3 is hydrogen or an ester moiety.
An ester moiety includes alkyl; e.g. unsubstituted alkyl or substituted alkyl, e.g. by
aryl, such as benzyl, alkoxybenzyl, such as 4-methoxybenzyl, alkoxy, such as methoxymethyl; alkyloxycarbonyloxy; alkyl; alkoxy, such as glycyloxy, phenylglycyloxy, e.g. glycyloxymethyl, phenylglycyloxymethyl; heterocyclyl e.g. 5-methyl-2-oxo-1,3-dioxolen-4-yl;
indanyl, phthalidyl, alkoxycarbonyloxy and ester moieties which form with the COOxe2x80x94 group a physiologically hydrolysable and acceptable ester, e.g. such known to be hydrolysable ester groups in the field of cephalosporins. A compound of formula I may thus be in the form of an physiologically-hydrolysable and -acceptable ester. By physiologically-hydrolysable and -acceptable esters as used herein is meant an ester in which the COOxe2x80x94 group is esterified and which is hydrolysable under physiological conditions to yield an acid which is itself physilogically tolerable at dosages to be administered. The term is thus to be understood as defining regular pro-drug forms. An ester moiety may be preferably a group which is easily hydrolysable under physiological conditions. Such esters may be administered preferably orally.
Parenteral administration may be indicated if the ester per se is an active compound or, if hydrolysis occurs in the blood.
In a compound of formula I:
V denotes preferably NO.
R1 denotes preferably hydrogen or alkyl, e.g. lower alkyl, e.g. including unsubstituted alkyl and substituted alkyl; e.g. by halogen, carboxyl, preferably by halogen.
R2 denotes preferably a group of formula a), axe2x80x2), c), d), dxe2x80x2), exe2x80x2) or f);
R4 denotes preferably hydrogen or alkyl, e.g. lower alkyl.
X and Y independently of each other denote preferably alkylene or alkenylene, e.g. (C1-4)alkylene or (C1-4)alkenylene, such as (C2-3)alkylene or (C2-3)alkenylene, e.g. including unsubstituted and substituted alkylene or alkenylene, e.g. by
halogen, alkyl, e.g. lower alkyl; cycloalkyl, carboxyl or alkylcarbonyl; preferably by alkyl, e.g. including hydroxyalkyl, aminoalkyl; carboxyl and (lower alkyl)carbonyl.
R5 denotes preferably hydrogen, alkyl, e.g. including unsubstituted alkyl and substituted alkyl, e.g. by
hydroxy, carboxyl, amino, e.g. including lower alkylamino or di-lower alkylamino; heterocyclyl, e.g. including 5 or 6 ring members and including one or two heteroatoms, e.g. one, e.g. selected from O, S and N; an ester of a carboxylic-, sulfonic- or phosphoric acid, e.g. an alkyl or aryl ester, e.g. wherein the carboxylic acid part contains 1 to 12 carbon atoms and wherein the ester part contains 1 to 8 carbon atoms; or
amino-iminomethyl, e.g. of formula 
wherein R11 and R12 independently of each other denote hydrogen or alkyl, e.g. lower alkyl,
R6 denotes preferably hydrogen; amino, alkylamino, dialkylamino, e.g. wherein the alkyl part is unsubstituted or substituted, e.g. by hydroxy, amino; arylamino; e.g. R6 denotes a group of formula xe2x80x94NR9R10, wherein R9 and R10 independently of each other denote hydrogen, alkyl, e.g. including hydroxyalkyl, aminoalkyl, aryl;
alkyl, e.g. including unsubstituted alkyl and substituted alkyl, e.g. by
heterocyclyl, e.g. having 5 to 6 ring members and one or two heteroatoms, e.g. selected from N,O,S; e.g. including unsubstituted heterocyclyl and substituted heterocyclyl; e.g. by hydroxy;
hydroxy; alkoxy, e.g. including unsubstituted alkyoxy and substituted alkoxy, e.g. by hydroxy, alkoxy, amino;
guanidino, e.g. wherein the amine groups are unsubstituted or substituted, e.g. the terminal amine group is part of heterocyclyl;
amino, alkylamino, and dialkylamino, e.g. (lower alkyl)amino and (lower dialkyl)amino;
alkyl, e.g. lower alkyl;
guanidino; wherein any amine group is unsubstituted or substituted, e.g. by alkyl; hydroxy, cycloalkyl, e.g. including unsubstituted and substituted cycloalkyl, e.g. by amino;
heterocyclyl, e.g. including heterocyclyl having 5 or 6 ring members and one or two heteroatoms, e.g. selected from N,O,S; including e.g. unsubstituted heterocyclyl and substituted heterocyclyl e. g. by alkyl, e.g. R6 denotes a group of formula xe2x80x94NR9xe2x80x2R10xe2x80x2, wherein R9xe2x80x2 and R10xe2x80x2 together with the nitrogen atom to which they are attached form heterocyclyl; or
a group of formula xe2x80x94Nxe2x95x90CHR8 wherein R8 preferably denotes aryl, heterocyclyl, including substituted and unsubstituted heterocyclyl; e.g. by alkyl; e.g. having 5 or 6 ring members and one or two heteroatoms, e.g. selected from N,O,S;
R5 and R6, if together with the nitrogen atoms to which they are attached form hetercyclyl, denote preferably alkylene, e.g. (C2-4)alkylene, such as (C2-3)alkylene;
Rxe2x80x26 denotes preferably alkyl, e.g. lower alkyl;
If R6 and R7 together with the nitrogen atom to which they are attached form hetercyclyl, hetercyclyl having preferably 5 to 7 ring members and one or two hetero atoms, e.g. selected from N,O,S.
In another aspect the present invention provides a compound of formula 
wherein W, R1, R3, R5 and R6 are as defined above.
In another aspect the present invention provides a compound of formula 
wherein W, R1, R3, R5 and R6 are as defined above and m denotes 1 or 2.
In another aspect the present invention provides the compound 7-{[(5-amino-1,2,4-thiadiazole-3-yl)-(Z)-(fluoromethoxyimino)acetyl]amino}-3-{[(3-ethyl-2-methylimino-imidazolidine-1-yl)imino]methyl}-3-cephem-4-carboxylic acid, e.g. in the form of a hydrochloride.
In this specification unless otherwise indicated terms such as xe2x80x9ccompound of formula I, Ia and Ibxe2x80x9d embrace the compound in any form, for example in the form of a salt and in free base form. The present invention thus includes a compound in free base form or, e.g. where such forms exist, in the form of a salt, for example in the form of an acid addition salt, inner salt, quaternary salt and/or in the form of a solvate, for example in the form of a hydrate. A salt may be a pharmaceutically acceptable salt of a compound of formula I, Ia and Ib, such as a metal salt or an amine salt. Metal salts include for example sodium, potassium, calcium, barium, zinc, aluminum salts, preferably sodium or potassium salts. Amine salts include for example trialkylamine, procaine, dibenzylamine and benzylamine salts. A free form of a compound of formula I, Ia and Ib may be converted into a salt form and vice versa.
In a further aspect the present invention provides a compound of formula I, Ia and Ib, in free form and in the form of a salt, for example an acid addition salt or a metal salt; and a compound of formula I, Ia and Ib e.g. in free form or in the form of a salt, in the form of a solvate.
If not otherwise stated herein any carbon containing group may contain up to 20 carbon atoms, e.g. alkyl includes, e.g. straight chain and branched, (C1-20), e.g. (C1-8)alkyl, such as (C1-6)alkyl and lower alkyl. Lower alkyl includes e.g. (C1-4)alkyl, such as (C1-2)alkyl. Cycloalkyl includes, for example (C3-7)cycloalkyl, particularly C3, C5 or C6 cycloalkyl. Acyl includes alkylcarbonyl and arylcarbonyl, e.g. (C1-12)acyl, e.g. (C1-6)acyl, such as (C1-4)acyl. Aryl includes phenyl, naphthyl, e.g. phenyl. Heterocyclyl includes heterocyclyl having 4 to 7, e.g. 5 to 6 ring members and 1 to 3 nitrogen, sulphur and/or oxygen hetero atoms (N,O,S) including, for example, condensed heterocyclyl, such as for example benzthiazolyl. Amino includes a free amine group, e.g. in the form of a salt, alkylamino, dialkylamino and arylamino, and e.g. protected amino.
Guanidino includes a guanidino group wherein the 3 nitrogen atoms are unsubstituted or independently of each other are substituted, e.g. by alkyl.
If not otherwise stated any group mentioned herein may be unsubstituted or substituted, e.g. one fold or several fold, e.g. by groups which are conventional in xcex2-lactam chemistry, such as by
alkyl, e.g. xe2x80x94CF3, aryl, alkoxy, halogen, hydroxy, carboxyl, a sulphonic acid derivative, such as SO3H, a phospshoric acid derivative, acyl, amino; guanidino, heterocyclyl, e.g. pyridyl, oxo, thiono, mercapto, alkyl- or arylthio, imino, alkylimino, CHO.
Halogen includes fluoro, chloro, bromo and iodo.
The present invention includes a compound of formula I in any isomeric from in which it may exist. E.g. the configuration in group xe2x80x94Cxe2x95x90Vxe2x80x94R1, wherein Vxe2x80x94R1 denotes Nxe2x80x94O, may be syn [(Z)] and anti [(E)] and is preferably syn [(Z)]. E.g. geometric isomers may be obtained, e.g. during a production process of a compound of formula I, e.g. due to the presence of a xe2x80x94CXxe2x80x2xe2x95x90CXxe2x80x3xe2x80x94 double bond wherein Xxe2x80x2 and Xxe2x80x3 are groups which have a different meaning. E.g. a chiral carbon atom may be introduced, e.g. during a production process of a compound of formula I and corresponding stereoisomeric forms of a compound of formula I may be obtained, e.g a mixture of the individual stereoisomers, e.g. a racemate, or pure isostercoisomeric forms. Mixtures of isomers may be separated.
The present invention includes a compound of formula I in any tautomeric form. E.g. a compound of formula I, wherein
R2 is a group of formula a), wherein R5 is hydrogen, or
R2 is a group of formula d), wherein R5 or R6 is hydrogen may exist in a tautomeric form, e.g. as described below: 
In another aspect the present invention provides a compound of formula 
wherein
Wp denotes CH or N,
Vp denotes xe2x95x90CHxe2x80x94 oder xe2x95x90Nxe2x80x94Oxe2x80x94,
R1p denotes hydrogen, acyl, carboxyl, unsubstituted alkyl, or alkyl substituted by halogen or carboxyl,
R3p denotes hydrogen, an ester forming group or a cation,
R2p denotes a group of formula 
xe2x80x83wherein Xp and Yp are the same or different and each denote a xe2x80x94(CH2)n-group, wherein n denote a number from 2 to 5, and optionally one or two CH2-groups are replaced by a xe2x80x94CHxe2x95x90CHxe2x80x94 group and optionally one or more hydrogen atoms are replaced by halogen, alkyl, cycloalkyl, hydroxyalkyl, aminoalkyl, carboxyl or ethoxycarbonyl,
R4p denotes hydrogen, alkyl or hydroxyalkyl,
R5p denotes hydrogen, alkyl, (poly)hydroxyalkyl or aminoalkyl, wherein optionally the alkyl groups are additionally substituted by a functional group, e.g. a carboxyl acid residue, a sulphonic acid residue or a phosphoric acid residue,
R6p denotes hydrogen, alkyl, hydroxyalkyl, aminoalkyl, amino, hydroxy, alkoxyalkyl, cycloalkyl, a group Nxe2x95x90CHR8p, wherein
R8p denotes aryl or heteroaryl,
or a group xe2x80x94NR9pR10, wherein
R9p und R10p are the same or different and each denote hydrogen, alkyl, hydroxyalkyl or aryl or denote together with the nitrogen atom a saturated, unsubstituted heterocycle with 5 or 6 ring members with one or two nitrogen and/or oxygen atoms,
and
R7p denotes hydrogen, or
R7p and R6p denote together with the nitrogen atom a heterocycle with 5 to 7 ring members containing one or two nitrogen and/or oxygen atoms, with the proviso that,
if Wp denotes CH, Vp denotes xe2x95x90Nxe2x80x94Oxe2x80x94, R1p denotes hydrogen or methyl, R2p denotes a group of formula d) and R3p denotes hydrogen, R5p and R6p denote at the same time another group than hydrogen or methyl, in free form, or, where such forms exist, in the form of acid addition salts, inner salts, quaternary salts or hydrates thereof.
A compound of formula I may be produced e.g. as described below and in the examples, and e.g. analogously to a method as conventional in xcex2-lactam chemistry.
In another aspect the present invention provides a process for the production of a compound of formula I, comprising reacting a compound of formula 
wherein W, V and R1 are as defined above and
xcex1) Rb denotes hydroxy and Rc and Rd together denote a bond, or
xcex2) Rd denotes hydrogen, a cation, an ester forming group or a silyl group, and Rb and Rc together denote the oxo group,
in free form or in the form of an acid addition salt thereof with an amine of formula
R2xe2x80x94NH2xe2x80x83xe2x80x83III
wherein R2 is as defined above, e.g. desired (reactive) groups may be protected with protecting groups, e.g. as conventional in xcex2-lactam chemistry, which may be, or, which are split off under the reaction conditions, or after termination of the reaction described above. A compound of formula I wherein R3 denotes hydrogen may be converted into a compound of formula I, wherein R3 denotes an ester moiety, e.g. a carboxylic acid ester group, and vice versa, e.g. by a method analogously to a method as conventional. A compound of formula I may be isolated from the reaction mixture in conventional manner, e.g. analogously to a method as conventional.
E.g. a compound of formula I may be produced as follows:
A compound of formula II may be reacted in a solvent which is inert under the reaction conditions, e.g. a polar solvent, e.g. water and a mixture of water with a lower alcohol or dioxan, or a dipolar aprotic solvent, e.g. dimethylformamide, dimethylsulfoxyde, dimethylacetamide, preferably dimethylacetamide, or a mixture of individual solvents, e.g. as described above, e.g. dimethylacetamide with alcohol or water, e.g. at a temperature from xe2x88x9220 to 50xc2x0 C. with a compound of formula III. An appropriate, e.g. optimal pH may be adjusted, e.g. by addition of a base or an acid, e.g. an inorganic or an organic acid. A compound of formula I obtained may be isolated from the reaction mixture, e.g. analogously to a method as conventional, e.g. by addition of an anti-solvent to the reaction mixture or, e.g. by chromatography. If desired, any group, e.g. a reactive group, may be protected before reaction, e.g. by silyl protecting group technology in a suitable solvent, e.g. in a solvent which is inert under the reaction conditions, e.g. halogentad carbohydrates, e.g. dichloromethane, nitriles, such as acetonitrile, ethers, e.g. tetrahydrofurane, or dipolar aprotic solvents, e.g. dimethylformamide, including a mixture of individual solvents, e.g. as defined above. Protecting groups may be split off, e.g. by a deprotection method, e.g. a method as conventional.
Starting compounds are known or may be obtained by a method as conventional, e.g. analogously or e.g. as described in the examples. Starting compounds, e.g. in free form or in the form of a salt, e.g. in the form of a hydrochloride, of formula 
wherein Yxe2x80x2 denotes alkylene, e.g. (C2-3)alkylene,
Rxe2x80x25 denotes hydrogen, alkyl or alkylimino;
e.g. unsubstituted alkyl, alkyl substituted by
hydroxy,
carboxyl,
amino, e.g. including an amine group, alkylamino and dialkylamino;
heterocyclyl, e.g. having 5 or 6 ring members and one or two heteroatoms, selected from N,O,S, e.g. N, e.g. piperidino, pyrrolidino;
guanidino;
pyridylmethylimino;
Rxe2x80x36 denotes hydrogen, alkyl, hydroxy, alkoxy, cycloalkyl, amino or heterocyclyl;
e.g. alkylamino, hydroxyalkylamino, phenylamino; unsubsituted alkyl, alkyl substituted by
heterocyclyl, e.g. having 5 to 6 ring members and containing one or two hetero atoms, e.g. selected from N,O,S, e.g. N, e.g. piperazino, piperidino, pyridino, morpholino, pyridoxal; including unsubstituted heterocyclyl and substituted heterocyclyl, e.g. by alkyl;
amino, e.g. including an amine group, alkylamino, dialkylamino, hydroxyalkylamino, (di)aminoalkylamino;
hydroxy, hydroxyalkoxy, alkoxy, e.g. hydroxyalkoxy, alkoxyalkoxy, aminoalkoxyalkoxy;
guanidino, e.g. wherein the amine groups are unsubstituted or substituted, e.g. by alkyl; e.g. and guanidino wherein the terminal amino group is part of a heterocyclic ring system, e.g. having 5 to 6 ring members and one or two heteroatoms selected from N,O,S; at least from N;
alkyl, e.g. lower alkyl;
hetercyclyl, e.g. having 5 to 6 ring members and containing one or two hetero atoms, e.g. selected from N,O,S; (C3-7)cycloalkyl, e.g. unsubstituted cycloalkyl or substituted cycloalkyl by amino;
Rxe2x80x27 and Rxe2x80x28 independently of each other denote hydrogen, carboxyl, alkoxycarbonyl, or alkyl; e.g. lower alkyl, e.g. unsubstituted alkyl and substituted alkyl, e.g. by hydroxy;
Rxe2x80x2xe2x80x36 and Rxe2x80x3xe2x80x36 independently of each other denote alkyl, e.g. lower alkyl; or,
Rxe2x80x2xe2x80x36 and Rxe2x80x3xe2x80x36 together with the nitrogen atom to which they are attached denote heterocyclyl, e.g. having 5 to 6 ring members and containing one or two hetero atoms, e.g. selected from N,O,S; at least one N;
Rxe2x80x35 denotes alkyl, e.g. lower alkyl; or
Rxe2x80x35 and Rxe2x80x2xe2x80x36 together denote alkylene, e.g. (C2-3)alkylene;
Rxe2x80x2xe2x80x35 and Rxe2x80x2xe2x80x3xe2x80x36 independently of each other denote alkyl, e.g. lower alkyl;
Rxe2x80x3xe2x80x3xe2x80x36 and Rxe2x80x37 together with the nitrogen atom to which they are attached form heterocyclyl, e.g. having 5 or 6 ring members and one or two heteroatoms, e.g. selected from N,O,S, e.g. N;
Rxe2x80x24 and Rxe2x80x2xe2x80x3xe2x80x3xe2x80x36 independently of each other denote alkyl, e.g. lower alkyl; and
Hal denotes halogen, e.g. chloro, bromo;
with the proviso that a compound of formula IInt wherein Rxe2x80x25, Rxe2x80x27 and Rxe2x80x28 are hydrogen and Rxe2x80x36 is hydrogen, 2-(N-morpholino)ethyl, 3-(N,N-dimethylamino)propyl; (2-hydroxyethyl)amino or 2-hydroxyethyl is excluded, are novel.
In another aspect the present invention provides a compound of formula IInt, IIInt, IIIInt, IVInt, VInt or VIInt, wherein the residues are as defined above, with the proviso as stated above.
The compounds of formula I, hereinafter designated as xe2x80x9cactive compound(s) of the inventionxe2x80x9d exhibits pharmacological activity, e.g. beside low toxicity and are therefore useful as pharmaceuticals. In particular, the active compounds of the invention show antimicrobial, e.g. antibacterial, activity against e.g. gram negative and gram positive bacteria, e.g. gram positive bacteria such as Pseudomonas, e.g. Pseudomonas aeruginosa; Escherichia, e.g. Escherichia coli; Enterobacter, e.g. Enterobacter cloacae; Klebsiella, e.g. Klebsiella edwardsii, Klebsiella pneumoniae; Enterococcus, e.g. Enterococcus faecalis; Moraxella, e.g. Moraxell catarrhalis; Streptococcus, e.g. Streptococcus pneumoniae, Streptococcus pyogenes; and Staphylococcus, e.g. Staphylococcus aureus; in vitro in the Agar Dilution Test according to National Commitee for Clinical Laboratory Standards (NCCLS) 1993, Document M7-A3Vol.13, No. 25: xe2x80x9cMethods for dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobicallyxe2x80x94Third Edition, Approved Standardxe2x80x9d. The active compounds show an MIC (xcexcg/ml) in the Agar Dilution Test from about  less than 0.0125 to ca.  greater than 25.6. The active compounds of the invention show an surprising overall activity spectrum.
It has, for example, been determined that the MIC (xcexcg/ml) of the compound of Example 48 against, for example E. coli strains ATCC 35218 and ATCC 10536 is of  less than 0.0125; and against Enterobacter cloacae strains is of  less than 0.0125.
The active compounds of the invention are, therefore, useful for the treatment of microbial, e.g. bacterial diseases.
In another aspect the present invention provides a compound of claim 1 for use as a pharmaceutical, preferably as an antimicrobial agent, such as an antibiotic. In a further aspect the present invention provides a compound of claim 1 for use in the preparation of a medicament for the treatment of microbial diseases, for example of diseaeses caused by bacterias selected from Pseudomonas, Escherichia, Enterobacter, Kkebsiella, Enterococcus, Moraxella, Streptococcus and Staphylococcus.
In a further aspect the present invention provides a method of treatment of microbial diseases which comprises administering to a subject in need of such treatment an effective amount of a compound of formula I.
For this indication, the appropriate dosage will, of course, vary depending upon, for example, the compound of formula I employed, the host, the mode of administration and the nature and severity of the conditions being treated. However, in general, for satisfactory results in larger mammals, for example humans, an indicated daily dosage is in the range from about 0.05 to 5 g, for example 0.1 to about 2.5 g, of an active compound of the invention conveniently administered, for example, in divided doses up to four times a day.
An active compound of the invention may be administered by any conventional route, for example orally, e.g. in form of tablets or capsules, or parenterally in the form of injectable solutions or suspensions, e.g. in analogous manner to ceftazidime.
The compound 7-{[(5-amino-1,2,4-thiadiazole-3-yl)-(Z)-(fluoromethoxyimino)-acetyl]amino}-3-{[(3-ethyl-2-methylimino-imidazolidine-1-yl)imino]methyl}-3-cephem-4-carboxylic acid, (compound of Example 48) is the preferred compound of the invention for use as an antimicrobial agent.
It has, for example been determined that the MIC (xcexcg/ml) of the compound of Example 48 (tested in form of the hydrochloride) against, for example Klebsiella edwardsii, strain ATCC 10896 is ca. 0.8 whereas, for example ceftazidime shows an MIC (xcexcg/ml) of ca. 1.6. It is therefore, indicated that for the treatment of microbial diseases, e.g. bacterial diseases the preferred compounds of the invention may be administered to larger mammals, for example humans, by similar modes of administration at similar dosages than conventionally employed with ceftazidime.
The compounds of formula I may be administered in pharmaceutically acceptable salt form, e.g. acid addition salt form or base addition salt form or in the corresponding free forms, optionally in solvate form. Such salts exhibit the same order of activity as the free forms.
The present invention also provides pharmaceutical compositions comprising a compound of formula I in pharmaceutically acceptable salt form or free form in association with at least one pharmaceutical carrier or diluent. Such compositions may be manufactured in conventional manner.
The present invention provides in further aspects
a compound of formula I for use as a pharmaceutical in the treatment of microbial diseases caused by bacterias selected from Pseudomonas, Escherichia, Enterobacter, Klebsiella, Moraxella, Enterococcus, Streptococcus, Staphylococcus;
the use of a compound of formula I, or use of a pharmaceutical composition comprising a compound of formula I as a pharmaceutical and
a method of treatment of microbial diseases which comprises administering to a subject in need of such treatment an effective amount of a compound of formula I.